This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cyclophosphamide is the most commonly prescribed drug used for chemotherapy, but it like other chemotherapy drugs, has many adverse side effects such as altered or lost taste sensory abilities which can lead to malnutrition and poorer recovery. We are interested in what causes the changes in taste functions due to chemotherapy. We hypothesize that cyclophosphamide damages the DNA of stem cells or progenitor cells for new taste sensory cells. The cell cycle is arrested until the DNA repair is complete. Once repaired, new taste sensory cells are generated from the stem cells and taste sensations recover. To test this hypothesis, we propose four Specific Aims that will use a range of tools from behavioral techniques to molecular biology using a mouse model. We will use behavioral and molecular methods to assess the breadth of functional disruptions caused by cyclophosphamide. In addition we propose to study how the drug disrupts adult taste stem cell functioning and how the system recovers, including the role of the Sox family of genes. No previous work has been done in this area. Our work aims to fill some voids in the understanding of this often devastating side effect of chemotherapy.